Brain Basics BRAIN ON DRUGS What is your

Brain Basics

BRAIN ON DRUGS?

What is your nervous system?

Neurons “communicate” with each other using neurotransmitters

Neurotransmitters convey “messages” across the synapse

Dopamine/Opioids: Brain’s incentive reward systems

Activation of reward center produces a “wanting” and “liking” response

Natural events activate these reward systems

Natural Events Elevate Dopamine Levels SEX FOOD % of Basal DA Output NAc shell 150 100 50 Empty Box Feeding 200 150 100 15 10 5 0 0 0 60 120 Time (min) Di Chiara et al. , Neuroscience, 1999. 180 Copulation Frequency DA Concentration (% Baseline) 200 Female Present Sample Number 1 2 3 4 5 6 7 8 Fiorino and Phillips, J. Neuroscience, 1997. Mounts Intromissions Ejaculations

Some drugs activate your reward systems since they act on the same receptors

Drugs make your brain really happy…. . BUT only when your brain is on drugs. Normal Brain on Drugs

AMPHETAMINE DA DOPAC HVA 0 1 2 3 4 Time After Amphetamine Accumbens Caudate 150 100 0 1 2 3 hr Time After Nicotine COCAINE DA DOPAC HVA 200 100 0 5 hr 250 % of Basal Release 200 Accumbens 300 NICOTINE 250 0 400 % of Basal Release Accumbens 1100 1000 900 800 700 600 500 400 300 200 100 0 % of Basal Release Effects of Drugs on Dopamine Release 0 1 2 3 4 Time After Cocaine Accumbens 5 hr MORPHINE Dose (mg/kg) 0. 5 1. 0 2. 5 10 200 150 100 0 0 1 2 3 4 Time After Morphine 5 hr Di Chiara and Imperato, PNAS, 1988

Repeated use of drugs trigger compensatory processes and saturate the brain’s reward systems ü individual can become conditioned/habituated/adapted to the intense level of drug-induced pleasure (develops tolerance or sensitization) ü the normal level of natural rewards are no longer experienced as very pleasurable, and ü after chronic use, the brain’s reward systems becomes so changed that nothing is pleasurable – not even the drugs!

Homeostatic Changes to Postsynaptic Receptor Density as a Function of the Amount of Neurotransmitter Released Upregulation Downregulation

Chronic drug taking …. reorganizes the liking and wanting systems Brain on drugs after tolerance Brain on drugs for an extended period … drugs may no longer be pleasurable but you still want them…

Drugs can change your brain so that natural events are no longer pleasurable

The brain now has a disease… it’s a different brain under constant stress Addicted When the “switch” gets flips depends on …. your brain chemistry…. your drug history…. Normal and other factors

Even 80 days following detox, a methamphetamine user’s dopamine transporter system (right) hasn’t recovered to normal levels (left)

Cocaine has long lasting effects Normal Cocaine Abuser (10 da) Cocaine Abuser (100 da)

At high enough doses, Ecstasy destroys nerve fibers

DA Receptors and the Response to Methylphenidate (MP) Low DA receptor high low Dopamine receptor level High DA receptor As a group, subjects with low receptor levels found MP pleasant while those with high levels found MP unpleasant Adapted from Volkow et al. , Am. J. Psychiatry, 1999.

Drugs not only affect the brain, but also affect the body

Gross Brain Anatomy Forebrain Midbrain Hindbrain (Brainstem = Midbrain + Hindbrain - Cerebellum)

Hindbrain • Medulla • Pons • Cerebellum

Medulla • caudal end of brainstem; rostral end of spinal cord • connects rest of brain to spinal cord • life support functions (heart rate, respiration)

Pons • ventral side of cerebellum • levels of consciousness, sleep, • arousal, control of autonomic functions, • sleep, relay info to cerebellum

Cerebellum • coordination of voluntary movement • learning motor behaviors • involved in cognition • timing of motor output

Midbrain • rostral end of brainstem: reticular formation, superior/inferior colliculi • arousal, wakefulness • information modulation • source cells for some important neurotransmitters (biogenic amines)

Forebrain • • • Cerebral Cortex Thalamus Hypothalamus Basal Ganglia Limbic System

Thalamus • relays information from diverse areas to cerebral cortex • integrates sensory information • regulates sleep-wakefulness

Hypothalamus • homeostatic control (e. g. body temperature, cardiovascular system, food and water intake) • regulates autonomic and endocrine systems • Infundibulum connects hypothalamus to pituitary glands

Basal Ganglia • voluntary movement, posture

Limbic System • Medial Forebrain Bundle – collection of various nerves running upstream through midbrain – involved in reinforcement • Hippocampus • Amygdala • Nucleus Accumbens

Hippocampus • medial side of temporal lobe • consolidation of short term memory into more permanent memory • recollection of spatial relationships

Amygdala • inferior medial temporal lobe • emotional feelings, fear, behavior, perception

Nucleus Accumbens • very important in reinforcement and addiction • regulation of movement • cognitive aspects of motor control

5 HT 1 a receptor distribution Mu receptor distribution

Cerebral Cortex Frontal lobe Parietal lobe Temporal lobe Occipital lobe

Occipital Lobe • vision

Parietal Lobe • body sensation (touch, pain, etc. ) • speech reception • spatial relationships

Temporal Lobe • • hearing memory emotion vision

Frontal Lobe • • planned motor behavior speech production higher cognition social reasoning